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Chapter 5Post-Travel Evaluation

Persistent Travelers’ Diarrhea

Bradley A. Connor

Although most cases of travelers’ diarrhea are acute and self-limited, a certain percentage of travelers will develop persistent (>14 days) gastrointestinal symptoms (see Chapter 2, Travelers’ Diarrhea). The pathogenesis of persistent travelers’ diarrhea generally falls into 1 of the following broad categories: 1) persistent infection or coinfection with a second organism not targeted by initial therapy, 2) previously undiagnosed gastrointestinal disease unmasked by the enteric infection, or 3) a postinfectious phenomenon.

PERSISTENT INFECTION

Most cases of travelers’ diarrhea are the result of bacterial infection and are short-lived and self-limited. Travelers may experience prolonged diarrheal symptoms if they are immunosuppressed, are infected sequentially with diarrheal pathogens, or are infected with protozoan parasites. Parasites as a group are the pathogens most likely to be isolated from patients with persistent diarrhea, and their probability relative to bacterial infections increases with increasing duration of symptoms. Parasites may also be the cause of persistent diarrhea in patients already treated for a bacterial pathogen.

Giardia is by far the most likely persistent pathogen to be encountered. Suspicion for giardiasis should be particularly high when upper gastrointestinal symptoms predominate. Untreated, symptoms may last for months, even in immunocompetent hosts. The diagnosis can often be made through stool microscopy, antigen detection, or immunofluorescence. However, as Giardia infects the proximal small bowel, even multiple stool specimens may fail to detect it, and a duodenal aspirate may be necessary for definitive diagnosis. Given the high prevalence of Giardia in persistent travelers’ diarrhea, empiric therapy is a reasonable option in the clinical setting after negative stool microscopy and in lieu of duodenal sampling. Other intestinal parasites that may cause persistent symptoms include Cryptosporidium species, Entamoeba histolytica, Isospora belli, Microsporidia, Dientamoeba fragilis, and Cyclospora cayetanensis.

Individual bacterial infections rarely cause persistence of symptoms, although persistent diarrhea has been reported in children infected with enteroaggregative or enteropathogenic Escherichia coli and among people with diarrhea due to Clostridium difficile. C. difficile–associated diarrhea may follow treatment of a bacterial pathogen with a fluoroquinolone or other antibiotic, or may even follow malaria chemoprophylaxis. This is especially important to consider in the patient with persistent travelers’ diarrhea that seems refractory to multiple courses of empiric antibiotic therapy. The initial work-up of persistent travelers’ diarrhea should always include a C. difficile stool toxin assay. Treatment of C. difficile is with metronidazole, oral vancomycin, or fidaxomicin, although increasing reports of resistance to the first 2 drugs have been noted.

Persistent travelers’ diarrhea has also been associated with tropical sprue and Brainerd diarrhea. These syndromes are suspected to result from infectious diseases, but specific pathogens have not been identified. Tropical sprue is associated with deficiencies of vitamins absorbed in the proximal and distal small bowel and most commonly affects long-term travelers to tropical areas. Investigation of an outbreak of Brainerd diarrhea among passengers on a cruise ship to the Galápagos Islands of Ecuador revealed that diarrhea persisted from 7 to more than 42 months and did not respond to antimicrobial therapy.

UNDERLYING GASTROINTESTINAL DISEASE

In some cases, persistence of gastrointestinal symptoms relates to chronic underlying gastrointestinal disease or susceptibility unmasked by the enteric infection. Most prominent among these is celiac disease, a systemic disease manifesting primarily with small bowel changes. In genetically susceptible people, villous atrophy and crypt hyperplasia are seen in response to exposure to antigens found in wheat, leading to malabsorption. The diagnosis is made by obtaining serologic tests, including tissue transglutaminase antibodies. A biopsy of the small bowel showing villous atrophy confirms the diagnosis. Treatment is with a wheat (gluten)-free diet.

Idiopathic inflammatory bowel disease, both Crohn disease and ulcerative colitis, may be seen after acute bouts of travelers’ diarrhea. One prevailing hypothesis is that an initiating endogenous pathogen triggers inflammatory bowel disease in genetically susceptible people.

Depending on the clinical setting and age group, it may be necessary to do a more comprehensive search for other underlying causes of chronic diarrhea. Colorectal cancer should be considered, particularly in patients passing occult or gross blood rectally or with the onset of a new iron-deficiency anemia.

POSTINFECTIOUS PHENOMENA

In a certain percentage of patients who present with persistent gastrointestinal symptoms, no specific source will be found. Patients may experience temporary enteropathy following an acute diarrheal infection, with villous atrophy, decreased absorptive surface area, and disaccharidase deficiencies. This can lead to osmotic diarrhea, particularly when large amounts of lactose, sucrose, sorbitol, or fructose are consumed. Use of antimicrobial medications during the initial days of diarrhea may also lead to alterations in intestinal flora and diarrhea symptoms.

Occasionally, the onset of symptoms of irritable bowel syndrome (IBS) can be traced to an acute bout of gastroenteritis. IBS that develops after acute enteritis has been termed postinfectious (PI)-IBS. In the context of travelers’ diarrhea, PI-IBS has been newly defined by the Rome III criteria as recurrent abdominal pain or discomfort associated with ≥2 of the following features:

Improvement with defecation

Onset associated with a change in the frequency of stool

Onset associated with a change in form (appearance) of stool

To be labeled PI-IBS, these symptoms should follow an episode of gastroenteritis or travelers’ diarrhea if the work-up for microbial pathogens and underlying gastrointestinal disease is negative. The role of small intestinal bacterial overgrowth in the pathogenesis of PI-IBS, especially when gas and bloating predominate, is being investigated.

EVALUATION

Three or more stool examinations should be performed for ova and parasites, including acid-fast stains for Cryptosporidium, Cyclospora, and Isospora; Giardia antigen testing; C. difficile toxin assay; and a D-xylose absorption test to determine if nutrients are being properly absorbed. Patients may also be given empiric treatment for Giardia infection. If underlying gastrointestinal disease is suspected, an initial evaluation should include serologic tests for celiac and inflammatory bowel disease. Subsequently, other studies to visualize both the upper and lower gastrointestinal tracts, with biopsies, may be indicated.

MANAGEMENT

Although US travelers are unlikely to become dehydrated or malnourished due to persistent diarrhea, hydration and nutritional support are of foremost importance. Dietary modifications may help those with malabsorption. If stools are bloody or when disease is caused by C. difficile, antidiarrheal medications such as loperamide or diphenoxylate should not be used in children and should be used cautiously, if at all, in adults. Probiotic medications have been shown to reduce the duration of persistent diarrhea among children in some settings. Antimicrobial medications may be useful in treating persistent diarrhea caused by parasites. Additional management strategies will depend on the specific cause of persistent diarrhea.